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Polymorphism DNA sequence 12q24.1 linked to phenylalanine hydroxylase gene in population from Republic of Moldova

Author: Angela Gavriliuc
Degree:doctor of biology
Speciality: 03.00.15 - Genetics
Scientific adviser: Stanislav Groppa
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific consultant: Anatol Jacotă (decedat)
doctor habilitat, professor, Institute of Genetics, Physiology and Plant Protection of the ASM
Scientific council:


The thesis was presented on the 23 September, 2004
Approved by NCAA on the 23 December, 2004


Adobe PDF document0.38 Mb / in romanian


We investigated the frequency and molecular basis of phenylketonuria in Moldova. On the base of newborn-screening data, we found the frequency to be 1:9000. Was founded State Register of patients with phenylketonuria (PKU) and DNA samples bank obtained from the families with high risk for this pathology. We performed molecular-genetics analysis of the phenylalanine hydroxylase gene of 59 patients with classical PKU and 68 individuals from controls with analysis of alleles and genotypes of the polymorphic loci of PAH gene. Was calculated index of deviation of empiric and theoretic heterozygosity by VNTR, Msp I(a), Pvu I(a) I and Bgl II polymorphic loci of PAH gene in Moldavian population. Were determined significant differences of frequencies distribution between normal and mutant chromosomes (p<0,01). Was calculated standard coefficient of linkage disequilibrium of studied polymorphic loci with PAH gene mutations (∆st=0,18-0,35). Was analyzed informativity of studied polymorph loci for PKU diagnosis in Moldavian population (from 28% to 63,8%). Were investigated 8 of more frequent PAH gene mutations which in overall shared 67,6% of defective alleles: R408W (49%), P281L (5,1%), R261Q (3,4%), R252W (3,4%), IVS10nt546 (2,5%), R158Q (2,5%), IVS12nt1 (1,7%). As a result of study of polymorph haplotypes and PAH gene mutations was developed scheme of molecular-genetic diagnosis of phenylketonuria which allow determination of 97,7% of all cases of this pathology in Moldavian population.